Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats

Xin-yu CHEN; Lu-ping YANG; Ya-ling ZHENG; Yu-xi LI; Dong-ling ZHONG; Rong-jiang JIN; Juan LI

doi:10.1007/s11655-021-2883-y

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Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats

Acupuncture Research | Updated：2022-03-29

- Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats
- Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats
- Chinese Journal of Integrative Medicine 2022年28卷第4期页码：357-365
- Affiliations：
  
  1.School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu (610072),China
  2.Food Science and Nutrition School, University of Leeds,Leeds (LS2 9JT), UK
  3.Department of Rehabilitation, the Second People's Hospital of Chengdu, Chengdu (610072), China
  4.School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu (610072), China
- Author bio：
  
  Prof. LI Juan, E-mail: 785939016@qq.com
- Funds：
  
  the National Natural Science Foundation of China(81704137;82074516);Sichuan Science and Technology Department(2019YJ0331)
- DOI：10.1007/s11655-021-2883-y
  中图分类号：
- 纸质出版日期：2022-04，
  
  网络出版日期：2021-11-28，
  
  录用日期：2021-03-17
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Xin-yu CHEN, Lu-ping YANG, Ya-ling ZHENG, 等. Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(4):357-365.

Xin-yu CHEN, Lu-ping YANG, Ya-ling ZHENG, et al. Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(4):357-365.
Xin-yu CHEN, Lu-ping YANG, Ya-ling ZHENG, 等. Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(4):357-365. DOI： 10.1007/s11655-021-2883-y.

Xin-yu CHEN, Lu-ping YANG, Ya-ling ZHENG, et al. Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(4):357-365. DOI： 10.1007/s11655-021-2883-y.

摘要

目的:

研究电针 (EA) 的降压机制是否与通过调节磷酸肌醇3激酶 (PI3K) /蛋白激酶B (Akt) 和丝裂原活化蛋白激酶 (MAPK) 信号通路

减弱血管平滑肌细胞 (VSMC) 的表型转换有关.

方法:

将8只Wistar-ktoyo大鼠设为正常血压组 (正常组) . 采用随机数字表法将32只自发性高血压大鼠随机分为4组: 模型组、电针组、电针+PI3K拮抗剂组 (EA+P组) 和电针+p38 MAPK激动剂+细胞外信号调节激酶激动剂组 (EA+M组) (

= 8/组) . 电针组、EA+P组和EA+M组的自发性高血压大鼠接受电针治疗

每周5次

连续4周

而正常组和模型组的大鼠在相同条件下捆绑. 在第0周和第4周测量每只大鼠的收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP). 干预4周后

收集胸主动脉进行苏木精-伊红(HE)染色、免疫组化检测 VSMC表型转换的标志蛋白[收缩标记物α平滑肌肌动蛋白(α-SMA)和钙桥蛋白(calponin)以及合成标记物骨桥蛋白(OPN)]. 蛋白质印迹测量胸主动脉的α-SMA、calponin、OPN、PI3K、磷酸化-Akt (p-Akt)、Akt、p-p42/44 ERK、总p42/44 ERK、p-p38 MAPK和总p38 MAPK]

的蛋白表达.

Abstract

Objective:

To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways.

Methods:

Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group

an EA group

an EA+PI3K antagonist group (EA+P group)

and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (

=8/group). SHRs in EA group

EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks

while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP)

diastolic blood pressure (DBP)

and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention

thoracic aorta was collected for hematoxylin-eosin (HE) staining

immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA

calponin

OPN

PI3K

phosphorylated-Akt (p-Akt)

Akt

p-p42/44 ERK

total p42/44 ERK

p-p38 MAPK and total p38 MAPK]

Results:

EA significantly reduced SBP

DBP and MAP (

0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (

0.01). From results of immunohistochemistry and Western blot

EA increased the expression of α-SMA and calponin

and decreased the expression of OPN (

0.01). In addition

the expression of PI3K and p-Akt increased (

0.01)

while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (

0.01). However

these effects were reversed by PI3K antagonist

p38 MAPK agonist and ERK agonist.

Conclusions:

EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs

in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

关键词

Keywords

electroacupuncturehypertensionvascular smooth muscle cellsPI3K/Akt signaling pathwayMAPK signaling pathway

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